Healthy VolunteersPhase 1NCT02972255
A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7079901 and the Combination of RO7079901 With Meropenem in Adult Healthy Volunteers
A Phase 1 study testing RO7079901 and Meropenem in people with Healthy Volunteers, run by Hoffmann-La Roche at 2 sites in United States.
Trial summary
This is a randomized, double-blind, placebo-controlled, multiple-ascending dose (MAD) study that will evaluate the safety, tolerability and pharmacokinetics (PK) of RO7079901 and the combination of RO7079901 with meropenem in healthy volunteers. The study will consist of three parts (Part I, II, and III). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- RO7079901 and Meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 2 sitesUnited States
- Study dates
- 31 Oct 2016to 24 Mar 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male or healthy female of non-childbearing-potential
- A Body Mass Index (BMI) between 18.0 and 30.0 kilograms per square meter (kg/m^2) (inclusive) and a body weight of at least 45 kilograms (kg) at screening
- Negative urine drug and alcohol screen (barbiturates, benzodiazepines, methadone, amphetamines, methamphetamines, opiates, cocaine, cannabinoids, cotinine, and alcohol)
- Non-smokers, or former smokers, who have not smoked for at least 60 days prior to screening
Who cannot join
- Known history of any significant hypersensitivity or severe allergic reaction to any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams)
- History of any severe antibiotic-associated superinfections like Clostridium difficile colitis and/or frequent fungal vaginal infections
- Concurrent or history of clinically significant cardiovascular, hepatic, renal, endocrine, gastrointestinal, respiratory, psychiatric, neurologic, and/or hematological disorders
- A history or presence of malignancy (with the exception of successfully treated basal cell carcinoma); seizures, brain lesions or other significant neurological diseases
- Donation of blood (or loss of blood) greater than 500 milliliters (mL) within three months before screening
- History of Gilbert syndrome
- Any clinically significant concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the healthy volunteer in this study
- Positive test at screening of any of the following: Hepatitis A Virus Immunoglobulin M Antibody (HAV IgM Ab), Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus Ribonucleic Acid or Hepatitis C Virus Antibody (HCV RNA or HCVAb), or Human Immunodeficiency Virus Antibody (HIV Ab)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Covance Clinical Research Unit Inc.; Covance Gfi Research
Evansville, Indiana, 47710
Covance Clinical Research Unit, Inc
Madison, Wisconsin, 53704
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of RO7079901 Administered Intravenously Both Alone and in Combination With Meropenem in Adult Healthy Volunteers
This is a randomized, double-blind, placebo-controlled, multiple-ascending dose (MAD) study that will evaluate the safety, tolerability and pharmacokinetics (PK) of RO7079901 and the combination of RO7079901 with meropenem in healthy volunteers. The study will consist of three parts (Part I, II, and III). At each dose level/cohort, a total of 8 healthy volunteers will be randomized to receive active study drug or placebo in a 3:1 ratio.
- Conditions
- Healthy Volunteers
- Being tested
- RO7079901, Meropenem, RO7049389 Placebo, Meropenem Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RO7079901Drug
RO7079901 will be administered as per schedule described in individual arm.
MeropenemDrug
Meropenem will be administered as per schedule described in individual arm.
RO7049389 PlaceboOther
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.
Meropenem PlaceboOther
Placebo matching to meropenem will be administered as per schedule described in individual arm.
| Study group | Role | What they receive |
|---|---|---|
| Part I: RO7079901 | Experimental | Participants will be randomized in two dose cohorts to receive single dose of RO7079901 1000 and 2000 milligrams (mg) intravenous (IV) infusion on Days 1 through Day 7 every 8 hours (q8h), for a total of 19 doses, with the last dose administered on the morning of Day 7. Receives: Drug: RO7079901 |
| Part I: Placebo | Placebo comparator | Participants will be randomized in two dose cohorts to receive single dose of placebo matching to RO7079901 on Days 1 through Day 7 q8h, for a total of 19 doses, with the last dose administered on the morning of Day 7. Receives: Other: RO7049389 Placebo |
| Part II - Single Dose and Repeat Dose: RO7079901 | Experimental | Participants will be randomized in two dose cohorts to receive single dose of RO7079901 IV infusion at a dose above the previously studied dose levels in Part I (greater than [>] 2000 mg) on Day 1, with the option to extend to q8h dosing for 7 days (i.e., starting on Day 3 through Day 9); once PK, safety and tolerability have been confirmed up to 48 hrs after the single dose. Receives: Drug: RO7079901 |
| Part II - Single Dose and Repeat Dose: Placebo | Placebo comparator | Participants will be randomized in two dose cohorts to receive single dose placebo matching to RO7079901 on Day 1, with the option to extend to q8h dosing for 7 days (i.e., starting on Day 3 through Day 9); once PK, safety and tolerability have been confirmed up to 48 hrs after the single dose. Receives: Other: RO7049389 Placebo |
| Part III: RO7079901 + Meropenem | Experimental | Participants will be randomized in three dose cohorts to receive RO7079901 and Meropenem IV infusion in one of the 2 treatment sequences. Participants randomized to Sequence 1 will receive a single dose of 2000 mg meropenem IV infusion on Day 1. On Day 2, participants will receive a single dose of RO7079901 IV infusion. Participants randomized to Sequence 2 will receive a single dose of RO7079901 IV infusion on Day 1. On Day 2, participants will receive a single dose of 2000 mg meropenem IV infusion. Starting on Day 3 and continuing through Day 9 (i.e., for a total of 19 doses, last dose in the morning of Day 9) all participants will receive RO7079901 in combination with meropenem IV infusion q8h, regardless of sequence. Escalation to a maximum dose of RO7079901 5000 mg q8h may be considered on the basis of safety and tolerability data from the previous cohorts. Receives: Drug: RO7079901; Drug: Meropenem |
| Part III: RO7079901 Placebo + Meropenem Placebo | Placebo comparator | Participants will be randomized in three dose cohorts to receive RO7079901 and Meropenem matching placebos in one of the 2 treatment sequences. Participants randomized to Sequence 1 will receive a single dose of placebo matching to meropenem on Day 1. On Day 2, participants will receive a single dose of placebo matching to RO7079901. Participants randomized to Sequence 2 will receive a single dose of placebo matching to RO7079901 on Day 1. On Day 2, participants will receive a single dose of placebo matching to meropenem. Starting on Day 3 and continuing through Day 9 (i.e., for a total of 19 doses, last dose in the morning of Day 9) all participants will receive RO7079901 and meropenem matching placebos q8h, regardless of sequence. Receives: Other: RO7049389 Placebo; Other: Meropenem Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part I: Percentage of Participants With Adverse Events
Measured: From screening to the follow-up or early withdrawal visit (up to Day 15)
Part II: Percentage of Participants With Adverse Events
Measured: From screening to the follow-up or early withdrawal visit (up to Day 17)
Part III: Percentage of Participants With Adverse Events
Measured: From screening to the follow-up or early withdrawal visit (up to Day 17)
Part I: Maximum Observed Plasma Concentration (Cmax) of RO7079901
Measured: Pre-infusion (0-1 hour [hr]) (infusion duration: 90 minutes [min]), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Time to Reach Cmax (Tmax) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Area Under the Plasma Concentration-Time Curve From Time Zero Until End of Dosing Interval (AUC0-tau) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Rate Constant of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Half-Life (t1/2) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Total Clearance (CL) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Volume of Distribution at Steady State (Vss) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Cmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Tmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: AUC0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Rate Constant of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: t1/2 of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Cmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Tmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: AUC0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Rate Constant of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: t1/2 of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part II - Single Dose: Cmax of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Tmax of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-tau of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Terminal Elimination Rate Constant of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: t1/2 of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: CL of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Vss of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Cmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Tmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: t1/2 of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Cmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Tmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: t1/2 of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Repeat Dose: Cmax of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Tmax of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: AUC0-tau of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Terminal Elimination Rate Constant of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: t1/2 of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: CL of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Vss of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Cmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Tmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: AUC0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: t1/2 of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Cmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Tmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: AUC0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: t1/2 of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part I: Cumulative Amount of RO7079901 Excreted in Urine (Ae)
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae From Time 0 to End of the Dosing Interval (8 hrs) (Ae0-tau) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Percent of RO7079901 Dose Excreted in Urine (Ae%), Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Renal Clearance (CLr) of RO7079901, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part II - Single Dose: Ae of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae0-tau of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Repeat Dose: Ae of RO7079901
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae0-tau of RO7079901
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae of Metabolite RO7110880
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae0-tau of Metabolite RO7110880
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae of Metabolite RO7053802
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae0-tau of Metabolite RO7053802
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Measured: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Quantifiable Time-Point (AUC0-last) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-last of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-24h of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-inf of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-last of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-24h of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-inf of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Repeat Dose: AUC0-last of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-24h of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-inf of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-last of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-24h of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-inf of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-last of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-24h of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-inf of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II: Cumulative Amount of RO7079901 Excreted in Urine From Time 0 to 24 Hours (Ae0-24h)
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae% of RO7079901, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae0-24 of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae0-24 of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part III: Cmax of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: CL of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Vss of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Cmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Cmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Ae of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of RO7079901
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of RO7079901, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of RO7079901, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Metabolite RO7110880
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Metabolite RO7053802
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Secondary outcomes (30)
Part III: Cmax of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: CL of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Vss of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Cmax of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Ae of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Meropenem, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Meropenem, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Meropenem, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion on Day 3
Part III: CLr of Meropenem, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Open Ring Metabolite of Meropenem
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/Dose
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/AUC0-tau
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion on Day 3
Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/AUC0-24h
Measured: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2016 (estimated)
- Study start31 Oct 2016
- Primary completion24 Mar 2017
- Study completion24 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02972255
- Sponsor's protocol ID
- NP30052
- Status last verified
- May 2017
- First submitted
- 21 Nov 2016
- Last updated
- 19 May 2017
- Results posted
- No
Publications
Mallalieu NL, Winter E, Fettner S, Patel K, Zwanziger E, Attley G, Rodriguez I, Kano A, Salama SM, Bentley D, Geretti AM. Safety and Pharmacokinetic Characterization of Nacubactam, a Novel beta-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02229-19. doi: 10.1128/AAC.02229-19. Print 2020 Apr 21.
PubMed 32041717
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of RO7079901 Administered Intravenously Both Alone and in Combination With Meropenem in Adult Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02972255
- Acronym / sponsor ID
- NP30052
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 31 Oct 2016 (actual)
- Primary completion
- 24 Mar 2017 (actual)
- Study completion
- 24 Mar 2017 (actual)
- First posted
- 23 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, double-blind, placebo-controlled, multiple-ascending dose (MAD) study that will evaluate the safety, tolerability and pharmacokinetics (PK) of RO7079901 and the combination of RO7079901 with meropenem in healthy volunteers. The study will consist of three parts (Part I, II, and III). At each dose level/cohort, a total of 8 healthy volunteers will be randomized to receive active study drug or placebo in a 3:1 ratio.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part I: RO7079901 | Experimental | Drug: RO7079901Participants will be randomized in two dose cohorts to receive single dose of RO7079901 1000 and 2000 milligrams (mg) intravenous (IV) infusion on Days 1 through Day 7 every 8 hours (q8h), for a total of 19 doses, with the last dose administered on the morning of Day 7. |
| Part I: Placebo | Placebo comparator | Other: RO7049389 PlaceboParticipants will be randomized in two dose cohorts to receive single dose of placebo matching to RO7079901 on Days 1 through Day 7 q8h, for a total of 19 doses, with the last dose administered on the morning of Day 7. |
| Part II - Single Dose and Repeat Dose: RO7079901 | Experimental | Drug: RO7079901Participants will be randomized in two dose cohorts to receive single dose of RO7079901 IV infusion at a dose above the previously studied dose levels in Part I (greater than [>] 2000 mg) on Day 1, with the option to extend to q8h dosing for 7 days (i.e., starting on Day 3 through Day 9); once PK, safety and tolerability have been confirmed up to 48 hrs after the single dose. |
| Part II - Single Dose and Repeat Dose: Placebo | Placebo comparator | Other: RO7049389 PlaceboParticipants will be randomized in two dose cohorts to receive single dose placebo matching to RO7079901 on Day 1, with the option to extend to q8h dosing for 7 days (i.e., starting on Day 3 through Day 9); once PK, safety and tolerability have been confirmed up to 48 hrs after the single dose. |
| Part III: RO7079901 + Meropenem | Experimental | Drug: RO7079901, Drug: MeropenemParticipants will be randomized in three dose cohorts to receive RO7079901 and Meropenem IV infusion in one of the 2 treatment sequences. Participants randomized to Sequence 1 will receive a single dose of 2000 mg meropenem IV infusion on Day 1. On Day 2, participants will receive a single dose of RO7079901 IV infusion. Participants randomized to Sequence 2 will receive a single dose of RO7079901 IV infusion on Day 1. On Day 2, participants will receive a single dose of 2000 mg meropenem IV infusion. Starting on Day 3 and continuing through Day 9 (i.e., for a total of 19 doses, last dose in the morning of Day 9) all participants will receive RO7079901 in combination with meropenem IV infusion q8h, regardless of sequence. Escalation to a maximum dose of RO7079901 5000 mg q8h may be considered on the basis of safety and tolerability data from the previous cohorts. |
| Part III: RO7079901 Placebo + Meropenem Placebo | Placebo comparator | Other: RO7049389 Placebo, Other: Meropenem PlaceboParticipants will be randomized in three dose cohorts to receive RO7079901 and Meropenem matching placebos in one of the 2 treatment sequences. Participants randomized to Sequence 1 will receive a single dose of placebo matching to meropenem on Day 1. On Day 2, participants will receive a single dose of placebo matching to RO7079901. Participants randomized to Sequence 2 will receive a single dose of placebo matching to RO7079901 on Day 1. On Day 2, participants will receive a single dose of placebo matching to meropenem. Starting on Day 3 and continuing through Day 9 (i.e., for a total of 19 doses, last dose in the morning of Day 9) all participants will receive RO7079901 and meropenem matching placebos q8h, regardless of sequence. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy male or healthy female of non-childbearing-potential
- A Body Mass Index (BMI) between 18.0 and 30.0 kilograms per square meter (kg/m^2) (inclusive) and a body weight of at least 45 kilograms (kg) at screening
- Negative urine drug and alcohol screen (barbiturates, benzodiazepines, methadone, amphetamines, methamphetamines, opiates, cocaine, cannabinoids, cotinine, and alcohol)
- Non-smokers, or former smokers, who have not smoked for at least 60 days prior to screening
Key exclusion criteria (8 listed)
- Known history of any significant hypersensitivity or severe allergic reaction to any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams)
- History of any severe antibiotic-associated superinfections like Clostridium difficile colitis and/or frequent fungal vaginal infections
- Concurrent or history of clinically significant cardiovascular, hepatic, renal, endocrine, gastrointestinal, respiratory, psychiatric, neurologic, and/or hematological disorders
- A history or presence of malignancy (with the exception of successfully treated basal cell carcinoma); seizures, brain lesions or other significant neurological diseases
- Donation of blood (or loss of blood) greater than 500 milliliters (mL) within three months before screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RO7079901RO7079901 will be administered as per schedule described in individual arm. | Drug | Part I: RO7079901, Part II - Single Dose and Repeat Dose: RO7079901, Part III: RO7079901 + Meropenem |
| MeropenemMeropenem will be administered as per schedule described in individual arm. | Drug | Part III: RO7079901 + Meropenem |
| RO7049389 PlaceboPlacebo matching to RO7049389 will be administered as per schedule described in individual arm. | Other | Part I: Placebo, Part II - Single Dose and Repeat Dose: Placebo, Part III: RO7079901 Placebo + Meropenem Placebo |
| Meropenem PlaceboPlacebo matching to meropenem will be administered as per schedule described in individual arm. | Other | Part III: RO7079901 Placebo + Meropenem Placebo |
Primary outcome
Part I: Percentage of Participants With Adverse Events
Time frame: From screening to the follow-up or early withdrawal visit (up to Day 15)
Part II: Percentage of Participants With Adverse Events
Time frame: From screening to the follow-up or early withdrawal visit (up to Day 17)
Part III: Percentage of Participants With Adverse Events
Time frame: From screening to the follow-up or early withdrawal visit (up to Day 17)
Part I: Maximum Observed Plasma Concentration (Cmax) of RO7079901
Time frame: Pre-infusion (0-1 hour [hr]) (infusion duration: 90 minutes [min]), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Time to Reach Cmax (Tmax) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Area Under the Plasma Concentration-Time Curve From Time Zero Until End of Dosing Interval (AUC0-tau) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Rate Constant of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Half-Life (t1/2) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Total Clearance (CL) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Volume of Distribution at Steady State (Vss) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Cmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Tmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: AUC0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Rate Constant of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: t1/2 of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Cmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Tmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: AUC0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: Terminal Elimination Rate Constant of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part I: t1/2 of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 1; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Day 7
Part II - Single Dose: Cmax of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Tmax of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-tau of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Terminal Elimination Rate Constant of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: t1/2 of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: CL of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Vss of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Cmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Tmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: t1/2 of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Cmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Tmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Terminal Elimination Rate Constant of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: t1/2 of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Repeat Dose: Cmax of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Tmax of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: AUC0-tau of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Terminal Elimination Rate Constant of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: t1/2 of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: CL of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Vss of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Cmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Tmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: AUC0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: t1/2 of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Cmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Tmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: AUC0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: Terminal Elimination Rate Constant of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part II - Repeat Dose: t1/2 of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Days 1 and 9
Part I: Cumulative Amount of RO7079901 Excreted in Urine (Ae)
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae From Time 0 to End of the Dosing Interval (8 hrs) (Ae0-tau) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Percent of RO7079901 Dose Excreted in Urine (Ae%), Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Renal Clearance (CLr) of RO7079901, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part I: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8 hrs post-infusion start on Day 1; pre-infusion (0-1 hr), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 7
Part II - Single Dose: Ae of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae0-tau of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Single Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II - Repeat Dose: Ae of RO7079901
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae0-tau of RO7079901
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae% of RO7079901, Calculated as Ae0-tau/Dose
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae of Metabolite RO7110880
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae0-tau of Metabolite RO7110880
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae of Metabolite RO7053802
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae0-tau of Metabolite RO7053802
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Repeat Dose: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre- infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 and 9
Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Quantifiable Time-Point (AUC0-last) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-last of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-24h of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-inf of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-last of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-24h of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Single Dose: AUC0-inf of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hrs post infusion on Day 1
Part II - Repeat Dose: AUC0-last of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-24h of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-inf of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-last of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-24h of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-inf of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-last of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-24h of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II - Repeat Dose: AUC0-inf of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post infusion on Day 1; pre-infusion (0-1 hr) on Day 2
Part II: Cumulative Amount of RO7079901 Excreted in Urine From Time 0 to 24 Hours (Ae0-24h)
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae% of RO7079901, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae0-24 of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae0-24 of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part II: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Day 1
Part III: Cmax of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: CL of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Vss of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Cmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Cmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Ae of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of RO7079901
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of RO7079901, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of RO7079901, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of RO7079901, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: CLr of RO7079901, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Metabolite RO7110880
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Metabolite RO7110880, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Metabolite RO7110880, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: CLr of Metabolite RO7110880, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Metabolite RO7053802
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Metabolite RO7053802, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Metabolite RO7053802, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: CLr of Metabolite RO7053802, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
30 secondary outcomes
Part III: Cmax of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: CL of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Vss of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Cmax of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Tmax of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-tau of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: AUC0-last of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: AUC0-inf of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence)
Part III: Terminal Elimination Rate Constant of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: t1/2 of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hrs post-infusion on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0.5, 1, 1.5, 2, 3, 4, 6, 8 hrs post-infusion on Day 3
Part III: Ae of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Meropenem, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Meropenem, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Meropenem, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion on Day 3
Part III: CLr of Meropenem, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-tau of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae0-24h of Open Ring Metabolite of Meropenem
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion start on Day 3
Part III: Ae% of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/Dose
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-tau/AUC0-tau
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence) and 9; pre-infusion (0-1 hr), and 0-4, 4-8 hrs post-infusion on Day 3
Part III: CLr of Open Ring Metabolite of Meropenem, Calculated as Ae0-24h/AUC0-24h
Time frame: Pre-infusion (0-1 hr) (infusion duration: 90 min), and 0-4, 4-8, 8-12, 12-24 hrs post-infusion start on Days 1 or 2 (depending on treatment sequence)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2017.
- Derived from this study: PubMed 32041717Mallalieu NL, Winter E, Fettner S, Patel K, Zwanziger E, Attley G, Rodriguez I, Kano A, Salama SM, Bentley D, Geretti AM. Safety and Pharmacokinetic Characterization of Nacubactam, a Novel beta-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02229-19. doi: 10.1128/AAC.02229-19. Print 2020 Apr 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RO7079901 and Meropenem in people with Healthy Volunteers, run by Hoffmann-La Roche at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part I: Percentage of Participants With Adverse Events (time frame: From screening to the follow-up or early withdrawal visit (up to Day 15)). The study lists 161 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02972255, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2017.